Efficient solid acid-catalyzed preparation of 25-OH-ginsenoside Rf and its enhanced cardioprotective effects against doxorubicin-induced cardiotoxicity

Abstract

The conversion of ginsenoside Rf from Panax ginseng into its bioactive 25-OH derivative has significant potential for therapeutic applications. In this study, we first screened various solid acid catalysts for their ability to facilitate this conversion, aiming to improve reaction efficiency and simplify the process compared to traditional chemical and biocatalytic methods. The reaction process was systematically analyzed by both TLC and HPLC-MS, while the reaction product was unambiguously characterized through HRMS and NMR techniques. The reaction parameter for the optimal catalysts was optimized by response surface methodology, resulting in an average relative yield of 97.92% for 25-OH-Rf. The process was completed within 5 hours, representing the most efficient method for preparing 25-OH-Rf to date. Subsequently, the cardioprotective effects of Rf and 25-OH-Rf against DOX-induced cardiotoxicity were evaluated using the AC16 cell model. The experimental results demonstrated that 25-OH-Rf was more effective than Rf in neutralizing DOX-induced cardiotoxicity, with its effect on cell viability comparable to that of trapidil. Molecular mechanism studies revealed that both Rf and 25-OH-Rf mitigated the detrimental effects of DOX by inhibiting caspase-8-mediated apoptotic cascades and the RIPK1/RIPK3/MLKL signaling pathway, where 25-OH-Rf exhibited a stronger modulatory effect on key biomarkers. This study offers an efficient approach for producing 25-OH-Rf and provides evidence supporting the enhanced cardioprotective properties of this modification of Rf. The findings pave the way for the development of other 25-OH derivatives of dammarane-type ginsenosides aimed at enhancing their bioactivity.